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Pharmacokinetic and pharmacodynamic drug interactions of carbamazepine and glibenclamide in healthy albino Wistar rats.

Prashanth S, Kumar AA, Madhu B, Rama N, Sagar JV - J Pharmacol Pharmacother (2011)

Bottom Line: In single dose study the percentage reduction of blood glucose levels and glibenclamide concentrations of rats treated with both carbamazepine and glibenclamide were significantly increased when compared with glibenclamide alone treated rats and the mechanism behind this interaction may be due to inhibition of P-glycoprotein mediated transport of glibenclamide by carbamazepine, but in multiple dose study the percentage reduction of blood glucose levels and glibenclamide concentrations were reduced and it may be due to inhibition of P-glycoprotein mediated transport and induction of CYP2C9, the enzyme through which glibenclamide is metabolised.The possible interaction involves both P-gp and CYP enzymes.To investigate this type of interactions pre-clinically are helpful to avoid drug-drug interactions in clinical situation.

View Article: PubMed Central - PubMed

Affiliation: Vaagdevi College of Pharmacy, Vishwambara Educational Society, Ramnagar, Hanmakonda, Warangal - 506 001, A.P, India.

ABSTRACT

Aims: To find out the pharmacokinetic and pharmacodynamic drug interaction of carbamazepine, a protype drug used to treat painful diabetic neuropathy with glibenclamide in healthy albino Wistar rats following single and multiple dosage treatment.

Materials and methods: Therapeutic doses (TD) of glibenclamide and TD of carbamazepine were administered to the animals. The blood glucose levels were estimated by GOD/POD method and the plasma glibenclamide concentrations were estimated by a sensitive RP HPLC method to calculate pharmacokinetic parameters.

Results: In single dose study the percentage reduction of blood glucose levels and glibenclamide concentrations of rats treated with both carbamazepine and glibenclamide were significantly increased when compared with glibenclamide alone treated rats and the mechanism behind this interaction may be due to inhibition of P-glycoprotein mediated transport of glibenclamide by carbamazepine, but in multiple dose study the percentage reduction of blood glucose levels and glibenclamide concentrations were reduced and it may be due to inhibition of P-glycoprotein mediated transport and induction of CYP2C9, the enzyme through which glibenclamide is metabolised.

Conclusions: In the present study there is a pharmacokinetic and pharmacodynamic interaction between carbamazepine and glibenclamide was observed. The possible interaction involves both P-gp and CYP enzymes. To investigate this type of interactions pre-clinically are helpful to avoid drug-drug interactions in clinical situation.

No MeSH data available.


Related in: MedlinePlus

The comparison of mean ± SD percentage reduction of blood glucose-time profile of glibenclamide (3.6 mg/kg) following pretreatment with carbamazepine (90 mg/kg) by oral administration in healthy rats
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Figure 0002: The comparison of mean ± SD percentage reduction of blood glucose-time profile of glibenclamide (3.6 mg/kg) following pretreatment with carbamazepine (90 mg/kg) by oral administration in healthy rats

Mentions: The hypoglycemic activity of glibenclamide was enhanced in combination treated group than individual glibenclamide treated group (46.62±3.20% to 53.17±4.30%) at fourth hour of initial day of treatment. But in multiple dosages the combination produced less hypoglycemic activity with maximum reduction of 38.13±3.71% on 15th day at fourth hour and the results are shown in Figure 2.


Pharmacokinetic and pharmacodynamic drug interactions of carbamazepine and glibenclamide in healthy albino Wistar rats.

Prashanth S, Kumar AA, Madhu B, Rama N, Sagar JV - J Pharmacol Pharmacother (2011)

The comparison of mean ± SD percentage reduction of blood glucose-time profile of glibenclamide (3.6 mg/kg) following pretreatment with carbamazepine (90 mg/kg) by oral administration in healthy rats
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3117577&req=5

Figure 0002: The comparison of mean ± SD percentage reduction of blood glucose-time profile of glibenclamide (3.6 mg/kg) following pretreatment with carbamazepine (90 mg/kg) by oral administration in healthy rats
Mentions: The hypoglycemic activity of glibenclamide was enhanced in combination treated group than individual glibenclamide treated group (46.62±3.20% to 53.17±4.30%) at fourth hour of initial day of treatment. But in multiple dosages the combination produced less hypoglycemic activity with maximum reduction of 38.13±3.71% on 15th day at fourth hour and the results are shown in Figure 2.

Bottom Line: In single dose study the percentage reduction of blood glucose levels and glibenclamide concentrations of rats treated with both carbamazepine and glibenclamide were significantly increased when compared with glibenclamide alone treated rats and the mechanism behind this interaction may be due to inhibition of P-glycoprotein mediated transport of glibenclamide by carbamazepine, but in multiple dose study the percentage reduction of blood glucose levels and glibenclamide concentrations were reduced and it may be due to inhibition of P-glycoprotein mediated transport and induction of CYP2C9, the enzyme through which glibenclamide is metabolised.The possible interaction involves both P-gp and CYP enzymes.To investigate this type of interactions pre-clinically are helpful to avoid drug-drug interactions in clinical situation.

View Article: PubMed Central - PubMed

Affiliation: Vaagdevi College of Pharmacy, Vishwambara Educational Society, Ramnagar, Hanmakonda, Warangal - 506 001, A.P, India.

ABSTRACT

Aims: To find out the pharmacokinetic and pharmacodynamic drug interaction of carbamazepine, a protype drug used to treat painful diabetic neuropathy with glibenclamide in healthy albino Wistar rats following single and multiple dosage treatment.

Materials and methods: Therapeutic doses (TD) of glibenclamide and TD of carbamazepine were administered to the animals. The blood glucose levels were estimated by GOD/POD method and the plasma glibenclamide concentrations were estimated by a sensitive RP HPLC method to calculate pharmacokinetic parameters.

Results: In single dose study the percentage reduction of blood glucose levels and glibenclamide concentrations of rats treated with both carbamazepine and glibenclamide were significantly increased when compared with glibenclamide alone treated rats and the mechanism behind this interaction may be due to inhibition of P-glycoprotein mediated transport of glibenclamide by carbamazepine, but in multiple dose study the percentage reduction of blood glucose levels and glibenclamide concentrations were reduced and it may be due to inhibition of P-glycoprotein mediated transport and induction of CYP2C9, the enzyme through which glibenclamide is metabolised.

Conclusions: In the present study there is a pharmacokinetic and pharmacodynamic interaction between carbamazepine and glibenclamide was observed. The possible interaction involves both P-gp and CYP enzymes. To investigate this type of interactions pre-clinically are helpful to avoid drug-drug interactions in clinical situation.

No MeSH data available.


Related in: MedlinePlus